Quality-adjusted survival time without symptoms or toxicity of acalabrutinib with or without obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia.

Acalabrutinib monotherapy (A) and acalabrutinib plus obinutuzumab (A + O) demonstrated improved efficacy and safety versus chlorambucil plus obinutuzumab (C + O) among treatment-naive patients with chronic lymphocytic leukaemia (CLL) in the ELEVATE-TN trial. The relative risk-benefit at a median follow-up of 47 months was assessed using Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) methodology. Patient data were partitioned into 3 states: time with toxicity (TOX); time without symptoms or toxicity (TWiST); and time after relapse (REL). Mean Q-TWiST was estimated by summing the mean time in each state, multiplied by its respective utility weight. Patients receiving A or A + O experienced significantly longer Q-TWiST versus C + O when toxicity was defined as grade 3-4 adverse events (AEs) (41.79 vs 34.56 months; 42.07 vs 34.56 months) and grade 2-4 AEs (35.07 vs 30.64 months; 34.21 vs 30.64 months). Overall, patients with treatment-naive CLL treated with A or A + O experienced significant gains in Q-TWiST compared with C + O.

Cost-effectiveness of acalabrutinib regimens in treatment-naïve chronic lymphocytic leukemia in the United States.

BACKGROUND: Clinical outcomes in chronic lymphocytic leukemia (CLL) have improved with targeted therapy, including Bruton tyrosine kinase inhibitors such as acalabrutinib. METHODS: A semi-Markov model with three health states (progression-free, progressed disease, and death) estimated cost per quality-adjusted life-year (QALY) gained for acalabrutinib ± obinutuzumab vs chlorambucil + obinutuzumab in treatment-naive CLL (based on ELEVATE-TN). The model used direct costs and resource utilization from the US Medicare perspective and utility values sourced from literature. Sensitivity analyses tested the robustness of the model. RESULTS: Over a 30-year lifetime horizon, the model base case analysis suggested that acalabrutinib monotherapy had an incremental cost of $206,329 and 2.52 QALYs gained versus chlorambucil + obinutuzumab, resulting in an incremental cost-effectiveness ratio (ICER) of $81,960/QALY. Acalabrutinib + obinutuzumab had an incremental cost of $423,747 and 2.79 QALYs gained (ICER: $152,153/QALY). Probabilistic sensitivity analysis showed the probability of acalabrutinib monotherapy being cost-effective as 59% to 73% at a $100,000-to-150,000/QALY willingness-to-pay threshold; the probability of acalabrutinib + obinutuzumab being cost-effective ranged from 34% to 51%. CONCLUSIONS: Although the analysis is limited by uncertainty in postprogression survival outcomes, acalabrutinib monotherapy is likely cost-effective vs chlorambucil + obinutuzumab in treatment-naive CLL in the US Medicare setting.

Considerations for the Utility of Real-World Evidence Beyond Trial Data in Advanced NSCLC: The Case of Frontline Tyrosine Kinase Inhibitors.

Background: To extend the discussion on the use of real-world evidence (RWE) in conveying the clinical value of treatment beyond trial data, the primary objective of this study was to assess if efficacy gains in progression-free survival (PFS) observed in randomized controlled trials (RCT) correlate with efficacy gains in the real-world setting. For this, we assessed the treatment benefit of three tyrosine kinase inhibitors (TKIs) in aNSCLC. Methods: Using matched cohorts identified in the Flatiron Health database (2011-2020), we mimicked the following cohorts of TKI versus platinum-based chemotherapy (PBC) from the following trials: (1) erlotinib, EURTAC; (2) afatinib, LUX-Lung 3; and (3) crizotinib, PROFILE 1014. Time to treatment discontinuation (TTD) hazard ratio (HR) was used as a proxy for PFS HR, the primary endpoint in the selected RCTs. HRs were calculated via Cox proportional hazard models. Results: Overall, 1,118 patients were included across the three RWE cohorts. Frontline TKI regimens had statistically significantly better real-world TTD than their matched PBC comparator group (HR 0.37, 95% confidence interval [CI] 0.30-0.44 for erlotinib; HR 0.42, 95% CI 0.32-0.55 for afatinib; HR 0.37, 95% CI 0.26-0.53 for crizotinib). The benefit in real-world OS was not different between TKIs and PBC patients, attributed to a high proportion of switching to subsequent therapy. Study findings of relative treatment benefit (HR) for real-world TTD and OS were deemed similar to those for PFS and OS from the pivotal RCTs. Conclusion: The relative treatment effect, measured as real-world TTD HR over the long term, was similar to trial-based PFS HR, implying that the clinical benefit of aNSCLC treatments conveyed in trials translated into the clinical setting. This is important, given that OS data interpretation is limited, even with longer follow-up. Additionally, our RWE analysis endorses TTD as a relevant endpoint to measure clinical benefit.

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options.

BACKGROUND: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients. METHODS: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents. RESULTS: For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible. CONCLUSIONS: After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.

Characteristics of schools of pharmacy associated with a successful PGY1 residency match.

INTRODUCTION: The literature is limited related to school of pharmacy (SOP) characteristics that may impact a student's residency match success. Given the paucity of information, the aim of our study was to examine the association between multiple school specific characteristics and Post-Graduate Year 1 (PGY1) residency match rate. METHODS: PGY1 residency match data and SOP specific characteristics were obtained. The median aggregate match rate was used to categorize programs as high or low match rate. Univariate and multivariate analyses were conducted to assess the impact of SOP characteristics on match rate. RESULTS: Median match rates were 64% (2013), 63.25% (2014), and 64.25% (2015). Schools with >95% North American Pharmacist Licensure Examination® (NAPLEX®) pass rate and >15 funded faculty were more likely to have a high match rate. Private schools were less likely to have a high match rate when compared to public programs. CONCLUSION: SOP characteristics associated with a high likelihood of a successful PGY1 residency match were greater than 95% of NAPLEX® pass rate, more than 15 funded faculty members, and public school status.

Factors associated with use of disease modifying agents for rheumatoid arthritis in the National Hospital and Ambulatory Medical Care Survey.

OBJECTIVE: We examined the treatment patterns among adults with rheumatoid arthritis (RA) and identified factors influencing access to traditional and biological disease modifying antirheumatic drugs (DMARDs). METHODS: We analyzed visits recorded in the National Ambulatory Medical Care Survey from 2005 to 2014 with a RA diagnosis. The primary outcome was DMARD use (traditional and/or biological). We included prescriptions of all RA-related treatments such as traditional and biological DMARDs, glucocorticoids, gold preparations, immunosuppressants, and non-steroidal anti-inflammatory drugs. Covariates in the logistic regression models included age, gender, race/ethnicity, type of health care coverage, provider type, geographic region, and number of comorbidities. RESULTS: Among 1405 visits with a RA diagnosis, 60.4% (n = 807) were prescribed DMARDs and 23.8% (n = 334) biological DMARDs. In fully adjusted models, females have 1.57 times higher odds of any DMARD use (95% confidence interval (CI): 1.02-2.46). Also, Medicare beneficiaries as compared to privately insured have 2.31 times higher odds of receiving any DMARDs (95% CI: 1.40-3.82), while visits with specialist vs. general physician are 2.38 times more associated with any DMARD use (95% CI: 1.37-4.14). For biological DMARDs, Medicare beneficiaries were at 2.58 times higher odds (95% CI: 1.42-4.70) than privately insured, while visits with specialist are at 3.37 times higher odds than general physician (95% CI: 1.40-8.23). CONCLUSION: Visits with a specialist and Medicare beneficiaries were significantly associated with any DMARD or biological DMARD use. Additionally, contrary to prior evidence, race/ethnicity was not associated with any DMARD or biological DMARD use, which may indicate reduction in disparity of treatment access.

Evaluation of PCMH Model Adoption on Teamwork and Impact on Patient Access and Safety.

PURPOSE: Each of the participating patient-centered medical home (PCMH) received coaching and participated in learning collaborative for improving teamwork. The objective of the study was to assess the impact of trainings on patient-centered teamwork. METHODS: The Teamwork Perception Questionnaire (TPQ) was administered once in spring 2014 and then in fall 2015. The TPQ consists of 35 questions across 5 domains: mutual support, situation monitoring, communication, team structure, and leadership. Based on our objective we compared the frequencies of strongly agree/agree by domain. The difference was tested using chi-square test. We compared the scores on each domain (strongly agree/agree = 1; maximum score = 7) via Wilcoxon rank sum test. RESULTS: The response rate for this survey was n = 29 (80.6%) in spring 2014, and n = 31 (86.1%) in fall 2015. We found that the practice members significantly ( P < .05) strongly agreed/agreed more in fall 2015 than spring 2014 for characteristics-"staff relay relevant information in a timely manner" (64.5% vs 83.9%) and "staff follow a standardized method of sharing information when handing off patients" (67.7% vs 90.3%) under communication domain and for characteristic-"staff within my practice share information that enables timely decision making" (74.2% vs 90.3%). However, there was no statistical significant difference observed in the scores for the overall TPQ at the 2 time points. CONCLUSION: Despite the statistical insignificance, the observations in PCMHs across the spectrum of practices participating in the Maryland Multi-Payer Program demonstrated enhanced teamwork specifically in communication and in leadership. This we believe will continue to result in enhanced patient access to care and safety.